Swiergiel Artur H, Li Yaohui, Wei Zhong You, Dunn Adrian J
Department of Pharmacology, Toxicology and Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932, USA.
Neurochem Int. 2008 May;52(6):1220-5. doi: 10.1016/j.neuint.2008.01.002. Epub 2008 Jan 6.
Noradrenergic and corticotropin-releasing factor (CRF) neuronal systems within the brain have been implicated in stress and anxiety. Synaptic release of cerebral norepinephrine (NE) is increased during stress, and following intracerebral CRF administration. Benzodiazepines are commonly used anxiolytic drugs but information on their effects on the stress- and CRF-related release of NE is limited. We have used in vivo microdialysis to test the effects of the benzodiazepine, chlordiazepoxide (CDP) on the noradrenergic responses to footshock and intracerebroventricular CRF in the medial hypothalamus and the medial prefrontal cortex (PFM) of freely moving rats. Footshock (60 x 0.1-0.2 mA shocks in 20 min) significantly increased microdialysate concentrations of NE in the first sample collected after initiating the footshock. In the hypothalamus, microdialysate NE was augmented 64% above baseline. A second footshock session (100 min after the first footshock) increased microdialysate NE to 313% of the baseline. Thus the noradrenergic responses to footshock were enhanced by preceding footshocks. CRF (100 ng) administered into the locus coeruleus (LC) almost tripled microdialysate concentrations of NE in the PFM. CDP (5mg/kg, i.p.) had no statistically significant effects on the basal dialysate concentrations of NE, but it significantly attenuated both footshock- and CRF-induced increases in dialysate NE. CDP may exert a direct inhibitory effect on the noradrenergic neurons, alter the input to LC noradrenergic neurons, or alter the ability of CRF to activate the LC noradrenergic system.
大脑中的去甲肾上腺素能和促肾上腺皮质激素释放因子（CRF）神经元系统与应激和焦虑有关。在应激期间以及脑室内注射CRF后，大脑去甲肾上腺素（NE）的突触释放会增加。苯二氮䓬类药物是常用的抗焦虑药物，但关于它们对应激和CRF相关的NE释放的影响的信息有限。我们使用体内微透析技术来测试苯二氮䓬类药物氯氮卓（CDP）对自由活动大鼠下丘脑内侧和前额叶内侧皮质（PFM）中去甲肾上腺素能对足部电击和脑室内CRF反应的影响。足部电击（20分钟内60次0.1 - 0.2 mA电击）在开始电击后收集的第一个样本中显著增加了微透析液中NE的浓度。在下丘脑中，微透析液中的NE比基线水平增加了64%。第二次足部电击（第一次电击后100分钟）使微透析液中的NE增加到基线的313%。因此，先前的足部电击增强了对足部电击的去甲肾上腺素能反应。向蓝斑（LC）注射CRF（100 ng）几乎使PFM中微透析液中NE的浓度增加了两倍。CDP（5mg/kg，腹腔注射）对NE的基础透析液浓度没有统计学上的显著影响，但它显著减弱了足部电击和CRF诱导的透析液中NE的增加。CDP可能对去甲肾上腺素能神经元产生直接抑制作用，改变传入LC去甲肾上腺素能神经元的输入，或改变CRF激活LC去甲肾上腺素能系统的能力。
